The present invention, in some embodiments thereof, relates to methods of diagnosing and treating cancer and, more specifically breast cancer and brain cancer.
The process of alternative splicing is widely misregulated in cancer and many tumors express new splicing isoforms which are absent in the corresponding normal tissue. Many oncogenes and tumor suppressors are differentially spliced in cancer cells and it has been shown that many of these cancer-specific isoforms contribute to the transformed phenotype of cancer cells. However, the contribution of alternative splicing regulators to cancer development has been largely unknown. Only recently the first functional evidence showed that some splicing factors can act as potent oncogenes and are up-regulated in human cancers. hnRNP proteins are abundant RNA-binding proteins expressed in most human tissues. The hnRNP A/B family is a subset of hnRNP proteins with closely related sequences and a conserved modular structure. They can affect alternative splicing, frequently by antagonizing SR proteins, in part through the recognition of exonic splicing silencers (ESS) elements. Additional functions of these proteins in post-splicing events, such as mRNA trafficking, and replication and transcription of cytoplasmic RNA viruses, have also been reported. Recent studies have shown that hnRNP A1 also affects the maturation of specific miRNAs among them pre-miR-18a which is part of a cluster of miRNAs with oncogenic activity (oncomirs). Previous studies showed overexpression of hnRNP A1 and hnRNP A2/B1 in lung and breast cancer (Fielding P et al., Clin Cancer Res 1999; 5: 4048-52, Zhou J et al., Lung Cancer 2001; 34: 341-50). Moreover, knockdown of hnRNP A1 and A2/B1 in breast cancer cells induced apoptosis which was specific for cancer cells (Patry C et al., Cancer Res 2003; 63: 7679-88).
U.S. Patent Application Publication No. 2007/0212738 teaches method of assessing responsiveness of a cancer patient to an EGFR kinase inhibitor, wherein high expression levels of heterogeneous nuclear ribonucleoprotein A2/B1 correlate with a tumor that will respond less effectively to treatment with an EGFR kinase inhibitor.
U.S. Pat. No. 6,251,586 teaches methods of early diagnosis of breast cancer by analyzing expression levels of heterogeneous nuclear ribonucleoprotein A2/B1. In addition, U.S. Pat. No. 6,251,586 teaches methods of treating cancer by administering antisense oligonucleotides which are substantially complementary to heterogeneous nuclear ribonucleoprotein A2/B1.